Factor V Leiden thrombophilia

Factor V is part of the blood-clotting cascade. The Leiden variant makes clotting harder to switch off, raising the risk of vein clots, especially around surgery, immobility, pregnancy or estrogen use.

What Factor V Leiden does

Clotting is a controlled cascade, and Factor V is one of its accelerators. Normally, activated protein C switches Factor V off once a clot has formed. This variant changes the site where protein C cuts, so the off switch works poorly and clotting activity persists longer than it should.

The clinical name for that state is activated protein C resistance, and Factor V Leiden is by far its most common cause. It affects venous clots, in the legs and lungs, rather than arterial events like heart attacks.

How strong the evidence is

This is one of the most solidly established common risk variants in medicine. The catalogued association comes from a study of more than 1.5 million people with a p-value below 1e-1000, giving an odds ratio near 3 per copy for venous thromboembolism, and clinical literature places heterozygotes at roughly 3 to 8 times baseline risk and homozygotes considerably higher, in the range of 10 to 80 times, with first clots occurring at younger ages.

ClinVar lists it under venous thromboembolism, ischaemic stroke, recurrent pregnancy loss and Budd-Chiari syndrome, with 31 or more submitters.

Relative risk against absolute risk

Multiples of this size need a baseline to mean anything. Venous thromboembolism affects roughly 1 to 2 people per 1,000 per year in the general population and rises steeply with age, so tripling a small annual risk leaves it small in absolute terms for most carriers.

What changes the picture is circumstance. Surgery, hospital admission, immobility, long-haul travel, pregnancy and the weeks after birth, oestrogen-containing contraception or hormone therapy, active cancer and severe infection are when an inherited tendency turns into an event.

Oestrogen and pregnancy, the two situations worth discussing

Combined oral contraception raises clot risk on its own, and it raises it further in carriers. Published estimates of the combination vary widely, from around 10 to 15 times baseline in more conservative analyses up to 30 times in older ones, which is a real spread and a reason to treat any single number cautiously. Absolute risks in prospective data remain well under 1 event per 100 person-years.

Pregnancy and the postpartum period carry higher risk than contraception does. For women with homozygous Factor V Leiden or combined thrombophilias, reported risk is in the range of 1 in 20 to 1 in 100 pregnancies. None of this dictates a decision on its own, and all of it belongs in a conversation with a clinician who knows your history.

How common it is

In 1000 Genomes reference data, about 4.8% of European-ancestry individuals carry one copy and roughly 1 in 1,600 carry two. It is rare in South Asian and African-ancestry samples and effectively absent in East Asian ones, which is why thrombophilia genetics reads very differently across populations.

What this variant does not tell you

Prothrombin G20210A, the other common inherited clotting variant, is read separately on this site. The rarer and stronger inherited causes, deficiencies of antithrombin, protein C and protein S, need blood testing and sequencing, and antiphospholipid syndrome is acquired and autoimmune. A normal result here does not rule any of them out.

Professional guidelines do not recommend testing asymptomatic people in the general population for thrombophilia, because the result rarely changes management in the absence of a clot or a strong family history. Knowing it is most useful as context before surgery, pregnancy or starting oestrogen.

What each rs6025 genotype means

rs6025 has three possible genotypes: CC, CT and TT.

No clotting variant (rs6025 CC). You don't carry Factor V Leiden, the most common inherited clotting variant. From what this gene shows your blood's clotting off-switch works normally and your clot risk is at baseline.

Higher clot risk (rs6025 CT). You carry one copy of Factor V Leiden, a variant that makes it harder for your body to switch off clotting. This raises your risk of clots in the veins, especially during long immobility, surgery, pregnancy, or while using estrogen-containing birth control. Most carriers never have a clot, but it's useful to know in those situations.

High clot risk (rs6025 TT). You have two copies of Factor V Leiden, which more strongly raises the risk of vein clots because your clotting is harder to switch off. This is worth discussing with a doctor, particularly around surgery, pregnancy, long travel, or hormone use, where extra precautions can lower the risk.

Evidence & sources

Across global populations, fewer than 1% of people carry two copies of this variant, and about 96% carry none.

This variant appears in 13 published genetic studies: PubMed 22672568 · PubMed 25772935 · PubMed 26908601 · PubMed 28373160 · PubMed 31420334 · PubMed 31676865 · PubMed 33592630 · PubMed 35285134 · PubMed 36154123 · PubMed 36777996 · PubMed 38561338 · PubMed 39789286 · PubMed 41298473.

Common questions

I have Factor V Leiden. Do I need blood thinners? Carrying the variant without a clotting history is not usually a reason for long-term anticoagulation, since the bleeding risk of treatment has to be weighed against a risk that stays low in absolute terms. Short-term preventive measures around surgery, hospital stays or pregnancy are a different question and one for your clinician.

Can I take the contraceptive pill? Many carriers do, and many clinicians suggest alternatives. Combined oral contraception raises clot risk on its own and more so in carriers, with published combination estimates ranging from about 10 to 30 times baseline, so the decision depends on your absolute risk, your history and the alternatives available. It is a conversation, not a rule.

Should my children be tested? Testing children for adult-onset thrombophilia is generally discouraged, since nothing changes in childhood management and the information can wait until they can decide for themselves.

Related

Atrial fibrillation risk (4q25) · Crohn's disease susceptibility · HbA1c (blood sugar) · Prothrombin clotting variant · Rheumatoid arthritis · Uric acid / gout tendency · Venous thromboembolism (clots)